Evidence map›Paper›PMID 25411882›Full record

ArticleNature chemistry2014

5-Hydroxymethylcytosine is a predominantly stable DNA modification.

Martin Bachman, Santiago Uribe-Lewis, Xiaoping Yang, Michael Williams, Adele Murrell, Shankar Balasubramanian

Registry-linked trialAbstract read
In one paragraph

Article in Nature chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03336554 (Indentifying Epigenetic Biomarkers From Peripheral Blood of Osteosarcoma Patients Based on hMe-Seal Technique), which is not on this map. Cited by 300 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
300citing papers in PubMed, 2 pooled it
22.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03336554 unknown statusnot on this mapstarted 2017, after this paper: background citation

Indentifying Epigenetic Biomarkers From Peripheral Blood of Osteosarcoma Patients Based on hMe-Seal Technique

Typeobservational_patient_registrySponsorPeking University People's HospitalRan2017 to 2018Enrolled100ConditionsHistologic Response (Tumor Necrosis Rate), Objective Response Rate for Neoadjuvant Chemotherapy, ORR, Progression-free Survival, PFS, Overall Survival, OS
3 · Its place in the literature

Who cites it

300 citing papers in PubMed, 2 syntheses or guidelines pooled it, 597 citations in OpenAlex.

  1. Pooled it
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  6. Uncovering ParB-dependent and -independent subclasses of T-dioxygenases from bacteriophage.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  18. SCoTCH-seq reveals that 5-hydroxymethylcytosine encodes regulatory information across DNA strands.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  20. Article

240 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Martin Bachman1] Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK [2] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Santiago Uribe-LewisCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Xiaoping YangCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Michael WilliamsCancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
Adele Murrell1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
Shankar Balasubramanian1] Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK [2] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
University of Cambridge · GBCancer Research UK · GB

Funding

Cancer Research UK 11961Cancer Research UK 12488Cancer Research UK 6934Cancer Research UK A11961Wellcome Trust 099232
6 · The paper itself

Abstract

5-Hydroxymethylcytosine (hmC) is an oxidation product of 5-methylcytosine which is present in the deoxyribonucleic acid (DNA) of most mammalian cells. Reduction of hmC levels in DNA is a hallmark of cancers. Elucidating the dynamics of this oxidation reaction and the lifetime of hmC in DNA is fundamental to understanding hmC function. Using stable isotope labelling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry, we show that the majority of hmC is a stable modification, as opposed to a transient intermediate. In contrast with DNA methylation, which occurs immediately during replication, hmC forms slowly during the first 30 hours following DNA synthesis. Isotopic labelling of DNA in mouse tissues confirmed the stability of hmC in vivo and demonstrated a relationship between global levels of hmC and cell proliferation. These insights have important implications for understanding the states of chemically modified DNA bases in health and disease.

Indexed as

5-MethylcytosineAnimalsCell CycleCell ProliferationCytosineDNADNA MethylationHCT116 CellsHumansMCF-7 CellsMiceMice, Inbred C57BL5-hydroxymethylcytosine5-MethylcytosineCytosineDNA

Identifiers

PMID25411882
PMCPMC4382525
OpenAlexW2056607606

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.